The microenvironment around a solid tumor is generally hypoxic. The ratio of deoxygenated to oxygenated hemoglobin concentration in tissue surrounding a tumor is higher than that in healthy tissue. By measuring tissue oxygenation, the functional behavior of a tumor may be assessed. Tissue oxygenation status may also be used to assess the effectiveness of conventional or neoadjuvant chemotherapies and to determine disease progression and aid in prognosis.
Near-infrared (NIR) absorption spectroscopy is a technique that has been used to measure the relative amounts of oxygenated and deoxygenated hemoglobin in tissue. In the NIR spectral window of 600-1000 nm, photon propagation in tissues is dominated by scattering rather than absorption. To make accurate measurements of hemoglobin concentration in the target tissue, the absorbed and scattered fractions of photons have to be decoupled. However, with continuous wave NIR absorption spectroscopy, which employs steady-state illumination, it is usually difficult to separate the absorbed and scattered fractions of photons. Therefore, conventional methods of NIR absorption spectroscopy do not allow accurate measurements of oxygenated and deoxygenated hemoglobin concentrations in tissue surrounding a tumor. To remedy this, researchers have developed various time- and frequency-domain techniques to measure the scattered and absorbed fractions of photons independently, and thereby calculate more accurate values of absolute hemoglobin concentrations. These measurement techniques that allow absorption and scattering to be measured separately are collectively referred to as Diffuse Optical Spectroscopy (DOS). When the scattered and absorbed fractions of photons are used for spatial reconstruction of tissue, the techniques are referred to as Diffuse Optical Tomography (DOT).
While there are commercially available continuous-wave NIR DOS devices (e.g. INVOS™ oximetry system from Medtronic-Covidien, NIRO-200NX Near Infrared Oxygenation Monitor from Hamamatsu, etc.), frequency domain NIR DOS devices have not transitioned from research to real-world use due to added complexities of the frequency domain techniques. The frequency domain DOS devices that are currently used for research are generally bulky and expensive, and therefore, cannot be easily translated into medical equipment for use in real-world hospital settings or at the point-of-care.
Thus, there remains a need to develop miniaturized, low-cost frequency domain spectroscopy and tomography devices that can be applied for continuous tissue oxygenation measurements.